Project Summary There are over 10 trillion endothelial cells (EC) that line the vasculature of the human body and these are an important replicative niche for a subset of viral, bacterial and parasitic pathogens. Consequently, it makes sense that the immune system has mechanisms to monitor this extensive network for signs of infection. While it has been proposed that activated EC have an important role in mediating resistance to these organisms this is an idea that has been difficult to test in vivo because of: 1) lack of tractable in vivo systems to modify EC immune functions 2) the size of and dynamic flow within the vascular system that hinders the detection of rare immune processes and 3) a lack of understanding of whether there are T cells specialized to operate in this environment.